title: Acetylsalicylic Acid reduces the severity of dextran sodium sulfate-induced colitis and increases the formation of anti-inflammatory lipid mediators.
abstract: The role of non-steroidal anti-inflammatory drugs in inflammatory bowel disease is controversial, as they have been implicated in disease aggravation. Different from other cyclooxygenase inhibitors, acetylsalicylic acid (ASA) enhances the formation of anti-inflammatory and proresolution lipoxins derived from arachidonic acid as well as resolvins from omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA). In this study, we examined the effect of ASA on murine dextran sodium sulfate colitis. A mouse magnetic resonance imaging (MRI) protocol and post mortem assessment were used to assess disease severity, and lipid metabolites were measured using liquid chromatography-coupled tandem mass spectrometry. Decreased colitis activity was demonstrated by phenotype and MRI assessment in mice treated with ASA, and confirmed in postmortem analysis. Analysis of lipid mediators showed sustained formation of lipoxin A4 and an increase of DHA-derived 17-hydroxydocosahexaenoic acid (17-HDHA) after treatment with ASA. Furthermore, in vitro experiments in RAW264.7 murine macrophages demonstrated significantly increased phagocytosis activity after incubation with 17-HDHA, supporting its proresolution effect. These results show a protective effect of ASA in a murine colitis model and could give a rationale for a careful reassessment of ASA therapy in patients with inflammatory bowel disease and particularly ulcerative colitis, possibly combined with DHA supplementation.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Virchow-Hospital, Charité Medical School, Free and Humboldt-University of Berlin, 13353 Berlin, Germany ; Laboratory for Lipid Medicine and Technology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Köhnke
authors.forename: Beate
authors.initials: B
authors.lastname: Gomolka
authors.forename: Süleyman
authors.initials: S
authors.lastname: Bilal
authors.forename: Xiangzhi
authors.initials: X
authors.lastname: Zhou
authors.forename: Yanping
authors.initials: Y
authors.lastname: Sun
authors.forename: Michael
authors.initials: M
authors.lastname: Rothe
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Baumgart
authors.forename: Karsten H
authors.initials: KH
authors.lastname: Weylandt
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D001241:Aspirin / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D016264:Dextran Sulfate; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D005260:Female; D008055:Lipids / Q000096:biosynthesis*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D008055:Lipids; D004281:Docosahexaenoic Acids; D016264:Dextran Sulfate; C062894:17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid; D001241:Aspirin